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Summary: In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Here, we demonstrate that T-box transcription factor T-brain 1 (Tbr1) is expressed in two groups of morphologically and functionally distinct RGCs: the orientation-selective J-RGCs and a group of OFF-sustained RGCs with symmetrical dendritic arbors. When Tbr1 is genetically ablated during retinal development, these two RGC groups cannot develop. Ectopically expressing Tbr1 in M4 ipRGCs during development alters dendritic branching and density but not the inner plexiform layer stratification level. Our data indicate that Tbr1 plays critical roles in regulating the formation and dendritic morphogenesis of specific RGC types. : Little is known about how diversified retinal ganglion cell (RGC) subtypes develop. Using genetic and electrophysiological analyses, Kiyama et al. identify Tbr1 expression in two types of morphologically and functionally distinct OFF RGCs. Loss-of-function and gain-of-function studies show Tbr1 regulates the formation and dendritic morphogenesis of these cells. Keywords: Tbr1, RGC development, RGC subtype, J-RGC, Jam2, OFF-sustained RGC, OFF RGC, dendritic branching, dendritic morphogenesis

BACKGROUND AND OBJECTIVE: To describe the presentation and the authors' evolving management strategy for intraocular dissemination of uveal melanoma cells following radiotherapy during the past decade. PATIENTS AND METHODS: Patients with uveal melanoma who developed intraocular dissemination of pigmented cells following radiotherapy. Histopathology was available in two cases. RESULTS: Four patients underwent treatment for progressive intraocular dissemination of uveal melanoma cells at 9 to 41 months following I-125 plaque radiotherapy (three patients) or proton beam radiotherapy (one patient). Treatments included primary enucleation (one patient), vitrectomy followed later by enucleation (one patient), and vitrectomy followed by intravitreal chemotherapy (two patients). Enucleated eyes demonstrated diffuse invasion of intraocular tissues by viable melanoma cells. No patient has developed systemic metastasis to date. CONCLUSIONS: Intraocular dissemination of pigmented cells following radiotherapy for uveal melanoma should raise suspicion for viable invasive melanoma cells. Prompt vitrectomy with intravitreal chemotherapy can be effective in avoiding enucleation in selected cases. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:573–579.]

To determine if receiving a prescheduled appointment is associated with an increased likelihood of complying with follow-up eye care among individuals identified as at risk for glaucoma during community-based glaucoma screening in an urban underserved population. This study sampled 362 individuals aged ≥30 years without known glaucoma from low-income, predominantly black/Hispanic neighborhoods in New Haven, Connecticut presenting to one of twelve community-based glaucoma screening events from May 2010 to October 2012. A quasi-experimental design systematically assigned 63 individuals identified as at risk for glaucoma into either intervention or control group with a 1:2 ratio. Individuals in the control group (n = 41) received counseling on glaucoma and a recommendation for obtaining a follow-up appointment at the eye department of a local community health center, which offers affordable health services with income-adjusted fee discounts to uninsured, low-income patients. Those in the intervention group (n = 22) received the same counseling and a prescheduled appointment at the community health center. The overall rate of follow-up compliance within 3 months of screening was 30 % (41 % in the intervention group; 24 % in the control group). Multivariate logistic regression analysis adjusting for sex, age, ethnicity, health insurance status, car access, living situation, and smoking status found that follow-up compliance was significantly associated with intervention (adjusted odds ratio 4.8; 95 % confidence interval 1.1-20.9). Providing prescheduled appointments can improve follow-up compliance after community-based glaucoma screening. This finding may be potentially applicable to community-based health screening for other preventable diseases.

Obstructive sleep apnea (OSA) is a disorder characterized by repeated episodes of partial or complete closure of the upper airway during sleep. Airway closure results in respiratory effort-related arousals and fragmented sleep that cause daytime symptoms such as sleepiness, fatigue, and decreased concentration. During episodes of apnea, patients become hypoxemic and undergo arterial blood pressure surges and increased intracranial pressure.1 Current evidence suggests that inflammatory processes, oxidative stress and endothelial dysfunction may play roles in the pathogenesis of vascular complications in OSA.2 By itself and irrespective of common comorbid conditions like hypertension, OSA has been shown to be an independent risk factor for coronary artery disease, stroke and death.3,4 With the increasing prevalence of OSA and its implications for increased morbidity and mortality further research into ophthalmic associations is important. Several ophthalmic conditions have been thus far linked to OSA including glaucoma, floppy eyelid syndrome, nonarteritic anterior ischemic optic neuropathy (NAION), optic disc edema, and diabetic retinopathy severity.5–8 While no definitive mechanism for ophthalmic associations has been elucidated, the alterations in blood pressure and hypoxemia seen in patients with OSA have been proposed as possible etiologies for glaucoma, NAION, optic disc edema, and the degree of diabetic retinopathy. More recent work by Glacet-Bernard et al. examined the association between OSA and retinal vein occlusion.9 They found a higher than expected prevalence of OSA in patients with vein occlusion proposing the idea that OSA may be a risk factor for vein occlusion. Increased tortuosity of the retinal vasculature has been associated with diabetes, hypoxia, older age, hypertension, and elevated body mass index (BMI).10,11 As all of these aforementioned factors are also associated with OSA we hypothesized that patients with OSA will have alterations in their retinal vascular pattern. Our findings in this pilot study demonstrate increased retinal vascular tortuosity in OSA that appears to be independent of comorbid conditions like hypertension and diabetes.

Purpose To apply a previously published scleral fixation technique to secure one-piece acrylic intraocular lenses (IOLs) to the sclera. Methods Retrospective, consecutive, noncomparative case series. Results All patients (16 eyes of 15 patients) who underwent scleral fixation of 1-piece acrylic IOLs using the loop method from 2014 to 2016 were included. The mean follow-up was 8.1 months. Repositioning of dislocated 1-piece acrylic IOLs was performed in 8 eyes, a primary implantation in 5 eyes, and IOL exchange in 3 eyes. All IOLs remained well-centered postoperatively. The vision improved from an initial best-corrected visual acuity of 0.97 ± 0.74 logMAR (Snellen equivalent ≈20/190) to 0.47 ± 0.49 logMAR (≈20/60, P = 0.031) at the last follow-up. The postoperative complications were self-limited. Conclusion The previously reported scleral suture fixation technique can be readily applied to one-piece acrylic IOLs.

Adenosine is a signaling molecule produced during conditions that cause cellular stress or damage. This signaling pathway is implicated in the regulation of pulmonary disorders through the selective engagement of adenosine receptors. The goal of this study was to examine the involvement of the A(3) adenosine receptor (A(3)R) in a bleomycin model of pulmonary inflammation and fibrosis. Results demonstrated that A(3)R-deficient mice exhibit enhanced pulmonary inflammation that included an increase in eosinophils. Accordingly, there was a selective up-regulation of eosinophil-related chemokines and cytokines in the lungs of A(3)R-deficient mice exposed to bleomycin. This increase in eosinophil numbers was accompanied by a decrease in the amount of extracellular eosinophil peroxidase activity in lavage fluid from A(3)R-deficient mice exposed to bleomycin, an observation suggesting that the A(3)R is necessary for eosinophil degranulation in this model. Despite an increase in inflammatory metrics associated with A(3)R-deficient mice treated with bleomycin, there was little difference in the degree of pulmonary fibrosis. Examination of fibrotic mediators demonstrated enhanced transforming growth factor (TGF)-beta1 expression, but not a concomitant increase in TGF-beta1 activity. This was associated with the loss of expression of matrix metalloprotease 9, an activator of TGF-beta1, in alveolar macrophages and airway mast cells in the lungs of A(3)R-deficient mice. Together, these results suggest that the A(3)R serves antiinflammatory functions in the bleomycin model, and is also involved in regulating the production of mediators that can impact fibrosis.

Hypertension, carotid occlusive disease, diabetes, cardiac valvular disease, stroke, and peripheral vascular disease are common causes of ocular ischemic syndrome.

CRAO: Central retinal artery occlusion causes diffuse superficial retinal whitening leading to appearance of a cherry-red spot in the macula due to arteriolar constriction.

Idiopathic juxtafoveal telangiectasis (IJT) refers to a heterogeneous group of rare clinical conditions that entail telangiectatic changes of the juxtafoveal or parafoveal capillary network in one or both eyes.

Retinal arterial macroaneurysm (RAM) is the outpouching of the wall within the first three orders of the arterial tree. Leakage may occur from the aneurysm or from the surrounding capillaries. If the aneurysm ruptures, then hemorrhage at all levels is possible.

BRAO: Branch retinal artery occlusion causes superficial retinal whitening and edema along the distribution of ischemic branch of the retinal artery.

CRVO: central retinal vein occlusion causes diffuse retinal hemorrhages (blood and thunder) associated with tortuous retinal venous vasculature.

CLRAO: cilioretinal artery occlusion can be isolated in collagen vascular disorders, may occur secondary to the increased hydrostatic pressure associated with CRVO or with anterior ischemic optic neuropathy.

BRVO: branch retinal vein occlusion causes sectoral retinal hemorrhages with associated venous dilation/tortuosity.

Mutations in the β-globin gene result in erythrocytes that undergo sickling in response to hypoxic, acidotic, and hyperosmolar conditions. Sickled erythrocytes are not pliable thereby resulting in mechanical occlusion of arterioles. Arteriolar occlusion is at the core of sickle cell retinopathy as it causes both nonproliferative and proliferative disease.

Adenosine has been implicated in the pathogenesis of chronic lung diseases such as asthma and chronic obstructive pulmonary disease. In vitro studies suggest that activation of the A2B adenosine receptor (A2BAR) results in proinflammatory and profibrotic effects relevant to the progression of lung diseases; however, in vivo data supporting these observations are lacking. Adenosine deaminase-deficient (ADA-deficient) mice develop pulmonary inflammation and injury that are dependent on increased lung adenosine levels. To investigate the role of the A2BAR in vivo, ADA-deficient mice were treated with the selective A2BAR antagonist CVT-6883, and pulmonary inflammation, fibrosis, and airspace integrity were assessed. Untreated and vehicle-treated ADA-deficient mice developed pulmonary inflammation, fibrosis, and enlargement of alveolar airspaces; conversely, CVT-6883-treated ADA-deficient mice showed less pulmonary inflammation, fibrosis, and alveolar airspace enlargement. A2BAR antagonism significantly reduced elevations in proinflammatory cytokines and chemokines as well as mediators of fibrosis and airway destruction. In addition, treatment with CVT-6883 attenuated pulmonary inflammation and fibrosis in wild-type mice subjected to bleomycin-induced lung injury. These findings suggest that A2BAR signaling influences pathways critical for pulmonary inflammation and injury in vivo. Thus in chronic lung diseases associated with increased adenosine, antagonism of A2BAR-mediated responses may prove to be a beneficial therapy.

Adenosine, a signaling nucleoside, exhibits tissue-protective and tissue-destructive effects. Adenosine levels in tissues are controlled in part by the enzyme adenosine deaminase (ADA). ADA-deficient mice accumulate adenosine levels in multiple tissues, including the lung, where adenosine contributes to the development of pulmonary inflammation and chronic airway remodeling. The present study describes the development of pulmonary fibrosis in mice that have been genetically engineered to possess partial ADA enzyme activity and, thus, accumulate adenosine over a prolonged period of time. These partially ADA-deficient mice live for up to 5 mo and die from apparent respiratory distress. Detailed investigations of the lung histopathology of partially ADA-deficient mice revealed progressive pulmonary fibrosis marked by an increase in the number of pulmonary myofibroblasts and an increase in collagen deposition. In addition, in regions of the distal airways that did not exhibit fibrosis, an increase in the number of large foamy macrophages and a substantial enlargement of the alveolar air spaces suggest emphysemic changes. Furthermore, important proinflammatory and profibrotic signaling pathways, including IL-13 and transforming growth factor-β1, were activated. Increases in tissue fibrosis were also seen in the liver and kidneys of these mice. These changes occurred in association with pronounced elevations of lung adenosine concentrations and alterations in lung adenosine receptor levels, supporting the hypothesis that elevation of endogenous adenosine is a proinflammatory and profibrotic signal in this model.

This report describes a unique case of coexisting necrobiotic xanthogranuloma and chronic lymphocytic leukemia in a patient presenting with scleritis and uveitis. A 53-year-old Caucasian man diagnosed with anterior uveitis and scleritis for the prior year was referred to our uveitis clinic for further evaluation. Prior uveitis/scleritis workup performed by the referring ophthalmologist was negative. Examination demonstrated unilateral uveitis and posterior scleritis along with bilateral conjunctival lesions. Incisional biopsy of the conjunctiva was carried out. The excised tissue was sent fresh for histopathologic studies. Slit-lamp examination revealed bilateral yellow-white bulbar conjunctival lesions, 1+ conjunctival injection OU, stellate keratic precipitates OS with 25 cells per high-powered field. Funduscopic examination was significant for subretinal fluid OS. Conjunctival biopsy revealed necrobiotic xanthogranuloma and chronic lymphocytic leukemia. Systemic workup demonstrated paraproteinemia consistent with necrobiotic xanthogranuloma and a complete blood count consistent with leukemia. This case demonstrates an atypical presentation of necrobiotic xanthogranuloma and concomitant chronic lymphocytic leukemia presenting in the form of uveitis, scleritis, and conjunctival infiltration. Masquerade syndromes, such as necrobiotic xanthogranuloma and leukemia, must be kept in mind when treating patients with uveitis or scleritis with negative workups.

Advances in the diagnosis and treatment of retinoblastoma have vastly improved patient outcomes. In developed countries, the most common cause of death in patients with heritable retinoblastoma is now a second primary tumor occurring in retinoblastoma survivors; many of these second primaries can be avoided by the reduced use of radiation. Mesenchymal tumors including primitive neuroectodermal tumors, bone and soft tissue sarcomas, leiomyomas, lipomas, cutaneous melanomas, and gliomas are the most common types of the second primary tumors in retinoblastoma survivors. Osteogenic sarcoma is the most common type of second primary tumor particularly in younger patients.

PECAM-1 (CD31) is a member of the immunoglobin (Ig) superfamily of cell adhesion molecules whose expression is restricted to hematopoietic and vascular cells. PECAM-1 can recruit adapter and signaling molecules via its immunoreceptor tyrosine activation motif (ITAM), suggesting that PECAM-1 plays a role in signal transduction pathways. To study the involvement of PECAM-1 in signaling cascades in vivo, we used the major histocompatibility (MHC) I gene promoter to target ectopic PECAM-1 expression in transgenic mice. We noted an attenuation of mammary gland development at early stages of virgin ductal branching morphogenesis. STAT5a, a modulator of milk protein gene expression during lactation, was localized to the nuclei of ductal epithelial cells of 6-week-old virgin PECAM-1 transgenics, but not in control mice. This correlated with decreases in ductal epithelial cell proliferation and induction of p21, an inhibitor of cell cycle progression. Using in vitro model systems we demonstrated PECAM-1/STAT5a association and found that residue Y701 in PECAM-1's cytoplasmic tail is important for PECAM-1/STAT5 association and that PECAM-1 modulates increases in STAT5a tyrosine phosphorylation levels. We suggest that by serving as a scaffolding, PECAM-1 can bring substrates (STAT5a) and enzymes (a kinase) into close proximity, thereby modulating phosphorylation levels of selected proteins, as previously noted for β-catenin.

Transforming growth factor-β1(TGF-β1) is a potent inducer of extracellular matrix protein synthesis and a key mediator of renal fibrosis. However, the intracellular signaling mechanisms by which TGF-β1stimulates this process remain incompletely understood. In this report, we examined the role of a major stress-activated intracellular signaling cascade, belonging to the mitogen-activated protein kinase (MAPK) superfamily, in mediating TGF-β1responses in rat glomerular mesangial cells, using dominant-negative inhibition of TGF-β1signaling receptors. We first stably transfected rat glomerular mesangial cells with a kinase-deleted mutant TGF-β type II receptor (TβR-IIM) designed to inhibit TGF-β1signaling in a dominant-negative fashion. Next, expression of TβR-IIMmRNA was confirmed by Northern analysis. Cell surface expression and ligand binding of TβR-IIMprotein were demonstrated by affinity cross-linking with125I-labeled-TGF-β1. TGF-β1rapidly induced p38 MAPK phosphorylation in wild-type and empty vector (pcDNA3)-transfected control mesangial cells. Interestingly, transfection with dominant-negative TβR-IIMfailed to block TGF-β1-induced p38 MAPK phosphorylation. Moreover, dominant-negative TβR-IIMfailed to block TGF-β1-stimulated pro-α1(I) collagen mRNA expression and cellular protein synthesis, whereas TGF-β1-induced extracellular signal-regulated kinase (ERK) 1/ERK2 activation and antiproliferative responses were blocked by TβR-IIM. In the presence of a specific inhibitor of p38 MAPK, SB-203580, TGF-β1was unable to stimulate pro-α1(I) collagen mRNA expression in the control and TβR-IIM-transfected mesangial cells. Finally, we confirmed that both p38 MAPK activation and pro-α1(I) collagen stimulation were TGF-β1effects that were abrogated by dominant-negative inhibition of TGF-β type I receptor. Thus we show first demonstration of p38 MAPK activation by TGF-β1in mesangial cells, and, given the rapid kinetics, this TGF-β1effect is likely a direct one. Furthermore, our findings suggest that the p38 MAPK pathway functions as a component in the signaling of pro-α1(I) collagen induction by TGF-β1in mesangial cells.

Shedding of cell surface molecules, including growth factor receptors, provides a mechanism by which cells regulate signal transduction events. Here we show that platelet-endothelial cell adhesion molecule (PECAM)-1 is shed from the endothelial cell surface during apoptosis and accumulates in the culture medium as a approximately 100 kDa soluble protein. The cleavage mediating the shedding is matrix metalloproteinase (MMP) dependent, as GM6001, a broad-spectrum MMP inhibitor, inhibits PECAM-1 accumulation in the culture medium in a dose-responsive manner. In addition to the 100 kDa soluble fragment, PECAM-1 cleavage generates the formation of a truncated (Tr.) approximately 28 kDa molecule, composed of the transmembrane and the cytoplasmic PECAM-1 domains. Transfections of the full-length (Fl) and the Tr. PECAM-1 gene constructs into endothelial and nonendothelial cells were performed. We found 1) significantly more gamma-catenin and SHP-2 bound to the truncated than to the full-length PECAM-1; 2) stable expression of the truncated PECAM-1 in SW480 colon carcinoma cells resulted in a dramatic decrease in cell proliferation, whereas expression of comparable levels of the full-length PECAM-1 had no effect; 3) the decrease observed in cell proliferation is due, in part, to an increase in programmed cell death (apoptosis) and correlated with continuous caspase 8 cleavage and p38/JNK phosphorylation. These results support the intimate involvement of PECAM-1 in signal transduction cascades and also suggest that caspase substrates (e.g., PECAM-1) may possess distinct and unique functions on cleavage.

Sensitivity to anoxia varies tremendously among phyla and species. Most mammals are exquisitely sensitive to low concentrations of inspired oxygen, while some fish, turtles and crustacea are very resistant. To determine the basis of anoxia tolerance, it would be useful to utilize a model system which can yield mechanistic answers. We studied the fruit fly, Drosophila melanogaster, to determine its anoxia resistance since this organism has been previously studied using a variety of approaches and has proven to be very useful in a number of areas of biology. Flies were exposed to anoxia for periods of 5-240 min, and, after 1-2 min in anoxia, Drosophila lost coordination, fell down, and became motionless. However, they tolerated a complete nitrogen atmosphere for up to 4 h following which they recovered. In addition, a nonlinear relation existed between time spent in anoxia and time to recovery. Extracellular recordings from flight muscles in response to giant fiber stimulation revealed complete recovery of muscle-evoked response, a response that was totally absent during anoxia. Mean O(2) consumption per gram of tissue was substantially reduced in low O(2) concentrations (20% of control). We conclude from these studies that: (1) Drosophila melanogaster is very resistant to anoxia and can be useful in the study of mechanisms of anoxia tolerance; and (2) the profound decline in metabolic rate during periods of low environmental O(2) levels contributes to the survival of Drosophila. Copyright 1997 Elsevier Science Ltd. All rights reserved

Inflammation of the eye is often times seen in association with systemic inflammatory diseases. Understanding the various forms of ocular involvement in these conditions is important as untreated ophthalmic involvement can lead to severe vision loss. In addition to providing a basic framework for diagnosis and treatment, this review will highlight the ocular manifestations of the following systemic inflammatory conditions: rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, Sjögren's syndrome, polyarteritisnodosa, primary antiphospholipid syndrome, Behçet's syndrome, Kawasaki disease, Cogan's syndrome and relapsing polychondritis.

Adenosine is generated at sites of tissue injury where it serves to regulate inflammation and damage. Adenosine signaling has been implicated in the regulation of pulmonary inflammation and damage in diseases such as asthma and chronic obstructive pulmonary disease; however, the contribution of specific adenosine receptors to key immunoregulatory processes in these diseases is still unclear. Mice deficient in the purine catabolic enzyme adenosine deaminase (ADA) develop pulmonary inflammation and mucous metaplasia in association with adenosine elevations making them a useful model for assessing the contribution of specific adenosine receptors to adenosine-mediated pulmonary disease. Studies suggest that the A2Aadenosine receptor (A2AR) functions to limit inflammation and promote tissue protection; however, the contribution of A2AR signaling has not been examined in the ADA-deficient model of adenosine-mediated lung inflammation. The purpose of the current study was to examine the contribution of A2AR signaling to the pulmonary phenotype seen in ADA-deficient mice. This was accomplished by generating ADA/A2AR double knockout mice. Genetic removal of the A2AR from ADA-deficient mice resulted in enhanced inflammation comprised largely of macrophages and neutrophils, mucin production in the bronchial airways, and angiogenesis, relative to that seen in the lungs of ADA-deficient mice with the A2AR. In addition, levels of the chemokines monocyte chemoattractant protein-1 and CXCL1 were elevated, whereas levels of cytokines such as TNF-α and IL-6 were not. There were no compensatory changes in the other adenosine receptors in the lungs of ADA/A2AR double knockout mice. These findings suggest that the A2AR plays a protective role in the ADA-deficient model of pulmonary inflammation.

Angiogenesis is a feature of chronic lung diseases such as asthma and pulmonary fibrosis; however, the pathways controlling pathological angiogenesis during lung disease are not completely understood. Adenosine is a signaling molecule that has been implicated in the exacerbation of chronic lung disease and in the regulation of angiogenesis; however, the relationship between these factors has not been investigated. The current study utilized adenosine deaminase (ADA)-deficient mice to determine whether chronic elevations in adenosine in vivo result in pulmonary angiogenesis. Results demonstrate substantial angiogenesis in the tracheas of ADA-deficient mice in association with adenosine elevations. ADA replacement enzyme therapy resulted in a lowering of adenosine levels and reversal of tracheal angiogenesis, indicating that the increases in vessel number are dependent on adenosine elevations. Levels of the angiogenic chemokine CXCL1 (mouse functional homologue of human IL-8) were found to be elevated in an adenosine-dependent manner in the lungs of ADA-deficient mice. Neutralization of CXCL1 and its receptor, CXCR2, resulted in the inhibition of angiogenic activity, which suggests that CXCL1 signaling through the CXCR2 receptor mediated the observed increases in angiogenesis. Our findings suggest that adenosine plays an important role, via CXCL1, in the induction of pulmonary angiogenesis.

Purpose of review The chronic lung diseases, asthma and chronic obstructive pulmonary disease, are pulmonary disorders in which persistent inflammation and alterations in lung structure contribute to a progressive loss of lung function. Although the exact type of inflammation and damage in each disease is distinct, they share the common feature that they are chronic in nature. Despite efforts, little is known about the cellular and molecular mechanisms that drive the chronicity of these two diseases. This review will summarize important findings regarding the role of adenosine, a signaling nucleoside implicated in the pathogenesis of these two disorders. Recent findings Aerosolized adenosine induces bronchoconstriction in patients with asthma and chronic obstructive pulmonary disease primarily through the release of mast cell mediators. In this setting it can not only be used to aid in diagnosis but also to monitor patient responses to steroid therapy. Adenosine levels are elevated in the lungs of asthma patients, indicating greater flux through adenosine receptor signaling pathways. In-vitro studies have shown adenosine to access pathways leading to the genesis of chronic inflammation via the release of proinflammatory cytokines and chemokines. Animal studies demonstrate that merely elevating adenosine levels in the mouse is sufficient to induce a pulmonary phenotype with features of asthma and chronic obstructive pulmonary disease. Summary Identifying mediators regulating the chronic nature of asthma and chronic obstructive pulmonary disease is critical towards advancements in treatment options. Adenosine has been implicated in promoting the inflammation and airway remodeling seen in chronic lung disease and thus makes an attractive therapeutic target.